Topical corticosteroids, as a class, demonstrate anti-inflammatory, anti-pruritic and vasoconstrictive actions. They are generally used to relieve the redness, skin edema (swelling), itching, crusting, flaking, blistering, cracking, oozing and discomfort of psoriasis, atopic dermatitis (atopic eczema) and other pathologies of the skin like contact dermatitis, seborrheic dermatitis, xerotic eczema, discoid eczema, venous eczema, dermatitis herpetiformis, neurodermatitis or autoeczematization.
Commercially, topical corticosteroid products are available as ointments, creams, solutions, foams and lotions. The Food and Drug Administration (FDA), Center for Drug Evaluation and Research (CDER) Data Standards Manual, Dosage Form (version 08) defines ointment as “a semisolid dosage form, usually containing less than 20% water and volatiles and more than 50% hydrocarbons, waxes, or polyols as the vehicle, which is generally for external application to the skin or mucous membranes”; cream as “an emulsion, semisolid dosage form, usually containing more than 20% water and volatiles and/or less than 50% hydrocarbons, waxes, or polyols as the vehicle, which is generally for external application to the skin or mucous membranes”; and lotion as “an emulsion, liquid dosage form, which is generally for external application to the skin”.
Due to their physico-chemical properties lotions are more pleasant to be used (cosmetically accepted) to the end-user than ointments or creams, e.g. lotions are easily applied than ointments or creams and are typically used for the treatment of large body areas, to hair-covered skin and on the hairy scalp.
While the mechanisms of the anti-inflammatory effects are unclear, there appears to be a correlation between the therapeutic effects of corticosteroids and their vasoconstrictive potencies. Vasoconstrictor assays have been commonly used to compare and predict the relative therapeutic potencies of topically applied corticosteroids (McKenzie A. W., Stoughton R. B.: Method for comparing percutaneous absorption of steroids. Arch Dermatol 1962; 86: 608-610)
Mometasone furoate is a corticosteroid commonly used in the treatment of inflammatory skin disorders, allergic rhinitis (such as hay fever), and asthma. Mometasone furoate is a fine white to off-white powder that is insoluble in water, slightly soluble in octanol, and moderately soluble in ethyl alcohol. The exceptionally poor solubility of mometasone furoate is a limitation for the development of topical pharmaceutical compositions.
Different solvents have been used in order to develop topical pharmaceutical compositions containing mometasone furoate, either containing said mometasone furoate partially dissolved and partially suspended or containing the drug totally dissolved due to the presence of solubilizing agents.
Thus, U.S. Pat. No. 4,775,529 describes topical pharmaceutical compositions containing corticosteroids (including mometasone furoate) in a hydro-alcoholic base comprising a) 15-50 wt. % of propylene glycol, b) 20-40 wt. % of isopropyl alcohol, c) 20-60 wt. % of water, d) 0.1-3.0 wt. % of a thickening agent and e) a buffer to adjust the pH between 3.0 to 6.0. Other topical mometasone furoate/propylene glycol pharmaceutical compositions are disclosed in WO 9108733, WO2004105686 and WO2008126076.
On the other side, U.S. Pat. No. 4,808,610 discloses topical pharmaceutical compositions comprising a) 0.01-0.25% of mometasone furoate, b) 5-20% of hexylene glycol, c) 1.0-5.0% of water, d) 2.0-10.0% of white wax, e) 40-70% of white petrolatum and other ingredients. U.S. Pat. No. 4,808,610 indicates that when mometasone furoate is partially dissolved and partially suspended in propylene glycol based cream formulations, the resulting formulations do not possess the necessary efficacy; and when mometasone furoate is completely dissolved in oleyl alcohol/propylene glycol based cream formulations, the resulting formulations not only lack the required activity but also are irritant in a rabbit dermal test. Additionally, according to U.S. Pat. No. 4,808,610, formulations containing drug solubilizing agents may result in poor activity.
Finally, EP 1886686 describes topical pharmaceutical compositions comprising a) 0.01-0.2 wt. % of mometasone furoate, b) 10-90 wt. % of water and c) a combination of at least an aromatic alcohol and at least a solvent selected from two different groups, and e) optionally further additives. According to EP 1886686 the combination of the aromatic alcohol and the solvent increases the solubility of mometasone furoate avoiding its precipitation even in the case of increasing the water content.
Surprisingly, it has been found that topical pharmaceutical compositions comprising mometasone furoate suspended in hexylene glycol based formulations (i.e. topical pharmaceutical compositions comprising solid particles of mometasone furoate dispersed in hexylene glycol based formulations) are stable, exhibit an efficacy comparable to mometasone furoate compositions available in the market and, due to its physico-chemical properties, are easily applied to the skin (easy to spread on the skin), in particular to hair-covered skin, absorb rapidly, not being irritant to the skin and, as a result, being more pleasant to use to the general patient population.